Performance of a Nonlinear Magnetic Handheld Probe for Intraoperative Sentinel Lymph Node Detection: A Phantom Study.

OBJECTIVE: This study investigates the performance of the DiffMag handheld probe (nonlinear magnetometry), to be used for sentinel lymph node detection. Furthermore, the performance of DiffMag is compared with a gamma probe and a first-order magnetometer (Sentimag®, linear magnetometry). METHODS: The performance of all three probes was evaluated based on longitudinal distance, transverse distance, and resolving power for two tracer volumes. A phantom was developed to investigate the performance of the probes for a clinically relevant situation in the floor of the mouth (FOM). RESULTS: Considering the longitudinal distance, both DiffMag handheld and Sentimag® probe had comparable performance, while the gamma probe was able to detect at least a factor of 10 deeper. Transverse distances of 13, 11, and 51 mm were measured for the small tracer volume by the DiffMag handheld, Sentimag®, and the gamma probe, respectively. For the large tracer volume this was 21, 18, and 55 mm, respectively. The full width at half maximum, at 7 mm probe height from the phantom surface, was 14, 12, and 18 mm for the small tracer volume and 15, 18, and 25 mm for the large tracer volume with the DiffMag handheld, Sentimag®, and gamma probe, respectively. CONCLUSIONS: With a high resolving power but limited longitudinal distance, the DiffMag handheld probe seems suitable for detecting SLNs which are in close proximity to the primary tumor. In this study, comparable results were shown using linear magnetometry. The gamma probe reached 10 times deeper, but has a lower resolving power compared with the DiffMag handheld probe.

Urinary excretion kinetics of [177Lu]Lu-PSMA-617.

INTRODUCTION: For the implementation of suitable radiation safety measures in [177Lu]Lu-PSMA-617 therapy, additional insight into excretion kinetics is important. This study evaluates this kinetics in prostate cancer patients via direct urine measurements. METHODS: Both the short-term (up to 24 h, n = 28 cycles) and long-term kinetics (up to 7 weeks, n = 35 samples) were evaluated by collection of urine samples. Samples were measured on a scintillation counter to determine excretion kinetics. RESULTS: The mean excretion half-time during the first 20 h was 4.9 h. Kinetics was significantly different for patients with kidney function below or above eGFR 65 ml/min. Calculated skin equivalent dose in case of urinary contamination was between 50 and 145 mSv when it was caused between 0 and 8 h p.i.. Measurable amounts of 177Lu were found in urine samples up to 18 days p.i.. CONCLUSION: Excretion kinetics of [177Lu]Lu-PSMA-617 is especially relevant during the first 24 h, when accurate radiation safety measures are important to prevent skin contamination. Measures for accurate waste management are relevant up to 18 days.

Amplitude-based optimal respiratory gating in positron emission tomography in patients with primary lung cancer.

OBJECTIVES: Respiratory motion during PET imaging introduces quantitative and diagnostic inaccuracies, which may result in non-optimal patient management. This study investigated the effects of respiratory gating on image quantification using an amplitude-based optimal respiratory gating (ORG) algorithm. METHODS: Whole body FDG-PET/CT was performed in 66 lung cancer patients. The respiratory signal was obtained using a pressure sensor integrated in an elastic belt placed around the patient's thorax. ORG images were reconstructed with 50%, 35%, and 20% of acquired PET data (duty cycle). Lesions were grouped into anatomical locations. Differences in lesion volume between ORG and non-gated images, and mean FDG-uptake (SUVmean) were calculated. RESULTS: Lesions in the middle and lower lobes demonstrated a significant SUVmean increase for all duty cycles and volume decrease for duty cycles of 35% and 20%. Significant increase in SUVmean and decrease in volume for lesions in the upper lobes were observed for a 20% duty cycle. The SUVmean increase for central lesions was significant for all duty cycles, whereas a significant volume decrease was observed for a duty cycle of 20%. CONCLUSIONS: This study implies that ORG could influence clinical PET imaging with respect to response monitoring and radiotherapy planning. KEY POINTS: Quantifying lesion volume and uptake in PET is important for patient management. Respiratory motion artefacts introduce inaccuracies in quantification of PET images. Amplitude-based optimal respiratory gating maintains image quality through selection of duty cycle. The effect of respiratory gating on lesion quantification depends on anatomical location.

Variability in lutetium-177 SPECT quantification between different state-of-the-art SPECT/CT systems.

BACKGROUND: Quantitative SPECT imaging in targeted radionuclide therapy with lutetium-177 holds great potential for individualized treatment based on dose assessment. The establishment of dose-effect relations requires a standardized method for SPECT quantification. The purpose of this multi-center study is to evaluate quantitative accuracy and inter-system variations of different SPECT/CT systems with corresponding commercially available quantitative reconstruction algorithms. This is an important step towards a vendor-independent standard for quantitative lutetium-177 SPECT. METHODS: Four state-of-the-art SPECT/CT systems were included: Discovery™ NM/CT 670Pro (GE Healthcare), Symbia Intevo™, and two Symbia™ T16 (Siemens Healthineers). Quantitative accuracy and inter-system variations were evaluated by repeatedly scanning a cylindrical phantom with 6 spherical inserts (0.5 - 113 ml). A sphere-to-background activity concentration ratio of 10:1 was used. Acquisition settings were standardized: medium energy collimator, body contour trajectory, photon energy window of 208 keV (± 10%), adjacent 20% lower scatter window, 2 × 64 projections, 128 × 128 matrix size, and 40 s projection time. Reconstructions were performed using GE Evolution with Q.Metrix™, Siemens xSPECT Quant™, Siemens Broad Quantification™ or Siemens Flash3D™ algorithms using vendor recommended settings. In addition, projection data were reconstructed using Hermes SUV SPECT™ with standardized reconstruction settings to obtain a vendor-neutral quantitative reconstruction for all systems. Volumes of interest (VOI) for the spheres were obtained by applying a 50% threshold of the sphere maximum voxel value corrected for background activity. For each sphere, the mean and maximum recovery coefficient (RCmean and RCmax) of three repeated measurements was calculated, defined as the imaged activity concentration divided by the actual activity concentration. Inter-system variations were defined as the range of RC over all systems. RESULTS: RC decreased with decreasing sphere volume. Inter-system variations with vendor-specific reconstructions were between 0.06 and 0.41 for RCmean depending on sphere size (maximum 118% quantification difference), and improved to 0.02-0.19 with vendor-neutral reconstructions (maximum 38% quantification difference). CONCLUSION: This study shows that eliminating sources of possible variation drastically reduces inter-system variation in quantification. This means that absolute SPECT quantification for 177Lu is feasible in a multi-center and multi-vendor setting; however, close agreement between vendors and sites is key for multi-center dosimetry and quantitative biomarker studies.

Improving the Spatial Alignment in PET/CT Using Amplitude-Based Respiration-Gated PET and Patient-Specific Breathing-Instructed CT.

Appropriate attenuation correction is important for accurate quantification of SUVs in PET. Patient respiratory motion can introduce a spatial mismatch between respiration-gated PET and CT, reducing quantitative accuracy. In this study, the effect of a patient-specific breathing-instructed CT protocol on the spatial alignment between CT and amplitude-based optimal respiration-gated PET images was investigated. Methods: 18F-FDG PET/CT imaging was performed on 20 patients. In addition to the standard low-dose free-breathing CT, breath-hold CT was performed. The amplitude limits of the respiration-gated PET were used to instruct patients to hold their breath during CT acquisition at a similar amplitude level. Spatial mismatch was quantified using the position differences between the lung-liver transition in PET and CT images, the distance between PET and CT lesions' centroids, and the amount of overlap as indicated by the Jaccard similarity coefficient. Furthermore, the effect on attenuation correction was quantified by measuring SUVs, metabolic tumor volume, and total lesion glycolysis (TLG) of lung lesions. Results: All patients found the breathing instructions feasible; however, 4 patients had trouble complying with the instructions. In total, 18 patients were included. The average distance between the lung-liver transition between PET and CT was significantly reduced for breath-hold CT (1.7 ± 2.1 mm), compared with standard CT (5.6 ± 7.3 mm) (P = 0.049). Furthermore, the mean distance between the lesions' centroids on PET and CT was significantly smaller for breath-hold CT (3.6 ± 2.0 mm) than for standard CT (5.5 ± 6.5 mm) (P = 0.040). Quantification of lung lesion SUV was significantly affected, with a higher SUVmean when breath-hold CT (6.3 ± 3.9 g/cm3) was used for image reconstruction than for standard CT (6.1 ± 3.8 g/cm3) (P = 0.044). Though metabolic tumor volume was not significantly different, TLG reached statistical significance. Conclusion: Optimal respiration-gated PET in combination with patient-specific breathing-instructed CT results in an improved alignment between PET and CT images and shows an increased SUVmean and TLG. Even though the effects are small, a more accurate SUV and TLG determination is of importance for a more stable PET quantification, which is relevant for radiotherapy planning and therapy response monitoring.

Metal Artifact Reduction of CT Scans to Improve PET/CT.

In recent years, different metal artifact reduction methods have been developed for CT. These methods have only recently been introduced for PET/CT even though they could be beneficial for interpretation, segmentation, and quantification of the PET/CT images. In this study, phantom and patient scans were analyzed visually and quantitatively to measure the effect on PET images of iterative metal artifact reduction (iMAR) of CT data. Methods: The phantom consisted of 2 types of hip prostheses in a solution of 18F-FDG and water. 18F-FDG PET/CT scans of 14 patients with metal implants (either dental implants, hip prostheses, shoulder prostheses, or pedicle screws) and 68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA) PET/CT scans of 7 patients with hip prostheses were scored by 2 experienced nuclear medicine physicians to analyze clinical relevance. For all patients, a lesion was located in the field of view of the metal implant. Phantom and patients were scanned in a PET/CT scanner. The standard low-dose CT scans were processed with the iMAR algorithm. The PET data were reconstructed using attenuation correction provided by both standard CT and iMAR-processed CT. Results: For the phantom scans, cold artifacts were visible on the PET image. There was a 30% deficit in 18F-FDG concentration, which was restored by iMAR processing, indicating that metal artifacts on CT images induce quantification errors in PET data. The iMAR algorithm was useful for most patients. When iMAR was used, the confidence in interpretation increased or stayed the same, with an average improvement of 28% ± 20% (scored on a scale of 0%-100% confidence). The SUV increase or decrease depended on the type of metal artifact. The mean difference in absolute values of SUVmean of the lesions was 3.5% ± 3.3%. Conclusion: The iMAR algorithm increases the confidence of the interpretation of the PET/CT scan and influences the SUV. The added value of iMAR depends on the indication for the PET/CT scan, location and size/type of the prosthesis, and location and extent of the disease.

Performance of 3DOSEM and MAP algorithms for reconstructing low count SPECT acquisitions.

PURPOSE: Low count single photon emission computed tomography (SPECT) is becoming more important in view of whole body SPECT and reduction of radiation dose. In this study, we investigated the performance of several 3D ordered subset expectation maximization (3DOSEM) and maximum a posteriori (MAP) algorithms for reconstructing low count SPECT images. MATERIALS AND METHODS: Phantom experiments were conducted using the National Electrical Manufacturers Association (NEMA) NU2 image quality (IQ) phantom. The background compartment of the phantom was filled with varying concentrations of pertechnetate and indiumchloride, simulating various clinical imaging conditions. Images were acquired using a hybrid SPECT/CT scanner and reconstructed with 3DOSEM and MAP reconstruction algorithms implemented in Siemens Syngo MI.SPECT (Flash3D) and Hermes Hybrid Recon Oncology (Hyrid Recon 3DOSEM and MAP). Image analysis was performed by calculating the contrast recovery coefficient (CRC),percentage background variability (N%), and contrast-to-noise ratio (CNR), defined as the ratio between CRC and N%. Furthermore, image distortion is characterized by calculating the aspect ratio (AR) of ellipses fitted to the hot spheres. Additionally, the performance of these algorithms to reconstruct clinical images was investigated. RESULTS: Images reconstructed with 3DOSEM algorithms demonstrated superior image quality in terms of contrast and resolution recovery when compared to images reconstructed with filtered-back-projection (FBP), OSEM and 2DOSEM. However, occurrence of correlated noise patterns and image distortions significantly deteriorated the quality of 3DOSEM reconstructed images. The mean AR for the 37, 28, 22, and 17mm spheres was 1.3, 1.3, 1.6, and 1.7 respectively. The mean N% increase in high and low count Flash3D and Hybrid Recon 3DOSEM from 5.9% and 4.0% to 11.1% and 9.0%, respectively. Similarly, the mean CNR decreased in high and low count Flash3D and Hybrid Recon 3DOSEM from 8.7 and 8.8 to 3.6 and 4.2, respectively. Regularization with smoothing priors could suppress these noise patterns at the cost of reduced image contrast. The mean N% was 6.4% and 6.8% for low count QSP and MRP MAP reconstructed images. Alternatively, regularization with an anatomical Bowhser prior resulted in sharp images with high contrast, limited image distortion, and low N% of 8.3% in low count images, although some image artifacts did occur. Analysis of clinical images suggested that the same effects occur in clinical imaging. CONCLUSION: Image quality of low count SPECT acquisitions reconstructed with modern 3DOSEM algorithms is deteriorated by the occurrence of correlated noise patterns and image distortions. The artifacts observed in the phantom experiments can also occur in clinical imaging.

A 3D-printed anatomical pancreas and kidney phantom for optimizing SPECT/CT reconstruction settings in beta cell imaging using 111In-exendin.

BACKGROUND: Quantitative single photon emission computed tomography (SPECT) is challenging, especially for pancreatic beta cell imaging with 111In-exendin due to high uptake in the kidneys versus much lower uptake in the nearby pancreas. Therefore, we designed a three-dimensionally (3D) printed phantom representing the pancreas and kidneys to mimic the human situation in beta cell imaging. The phantom was used to assess the effect of different reconstruction settings on the quantification of the pancreas uptake for two different, commercially available software packages. METHODS: 3D-printed, hollow pancreas and kidney compartments were inserted into the National Electrical Manufacturers Association (NEMA) NU2 image quality phantom casing. These organs and the background compartment were filled with activities simulating relatively high and low pancreatic 111In-exendin uptake for, respectively, healthy humans and type 1 diabetes patients. Images were reconstructed using Siemens Flash 3D and Hermes Hybrid Recon, with varying numbers of iterations and subsets and corrections. Images were visually assessed on homogeneity and artefacts, and quantitatively by the pancreas-to-kidney activity concentration ratio. RESULTS: Phantom images were similar to clinical images and showed comparable artefacts. All corrections were required to clearly visualize the pancreas. Increased numbers of subsets and iterations improved the quantitative performance but decreased homogeneity both in the pancreas and the background. Based on the phantom analyses, the Hybrid Recon reconstruction with 6 iterations and 16 subsets was found to be most suitable for clinical use. CONCLUSIONS: This work strongly contributed to quantification of pancreatic 111In-exendin uptake. It showed how clinical images of 111In-exendin can be interpreted and enabled selection of the most appropriate protocol for clinical use.

Improving the Spatial Alignment in PET/CT Using Amplitude-Based Respiration-Gated PET and Respiration-Triggered CT.

UNLABELLED: Respiratory motion during PET can cause inaccuracies in the quantification of radiotracer uptake, which negatively affects PET-guided radiotherapy planning. Quantitative accuracy can be improved by respiratory gating. However, additional miscalculation of standardized uptake value (SUV) in PET images can be caused by inappropriate attenuation correction due to a spatial mismatch between gated PET and CT. In this study, the effect of respiration-triggered CT on the spatial match between CT and amplitude-based respiration-gated PET images is investigated. METHODS: (18)F-FDG PET/CT was performed in 38 patients. Images were acquired on 2 PET/CT scanners, one without and one with continuous bed motion during PET acquisition. The amplitude limits of the amplitude-based respiration-gated PET were used for the respiration-triggered sequential low-dose CT. Both standard (spiral) and triggered CT scans were used to reconstruct the PET data. Spatial mismatch was quantified using the position difference between the lung-liver boundary in PET and CT images, the distance between PET and CT lung lesions' centroids, and the amount of overlap of lesions indicated by the Jaccard similarity coefficient. Furthermore, the effect of attenuation correction was quantified by measuring SUVs in lung lesions. RESULTS: For triggered CT, the average distance between the lung-liver boundary in PET and CT was significantly reduced (4.5 ± 6.7 mm) when compared with standard CT (9.2 ± 8.1 mm) (P < 0.001). The mean distance between the lesions' centroids in PET and CT images was 6.3 ± 4.0 and 5.6 ± 4.2 mm (P = 0.424), for the standard and triggered CT, respectively. Similarly, the Jaccard similarity coefficient was 0.30 ± 0.21 and 0.32 ± 0.20 (P = 0.609) for standard and triggered CT, respectively. For 6 lesions, there was no overlap of PET and CT when the standard CT was used; compared with the triggered CT, these lesions showed (partial) overlap. The maximum and mean SUV increase of the PET/CT compared with the PET/triggered CT was 5.7% ± 11.2% (P < 0.001) and 6.1% ± 10.2% (P = 0.001), respectively. CONCLUSION: Amplitude-based respiration-gated PET in combination with respiration-triggered CT resulted in a significantly improved match in the area of the liver dome and a significantly higher SUV for lung lesions. However, lesions in the lungs did not show a consistent improvement in spatial match.

Comparison of a free-breathing CT and an expiratory breath-hold CT with regard to spatial alignment of amplitude-based respiratory-gated PET and CT images.

UNLABELLED: Respiratory motion during PET has a significant effect on the quantification of radiotracer uptake in PET images. Even when respiratory motion is considered using PET gating techniques, inaccuracies in standardized uptake values can be caused by inappropriate attenuation correction due to a spatial mismatch between PET and CT. In this study, the effect of breath-hold CT imaging on the spatial match between CT and amplitude-based respiratory-gated PET images is investigated. METHODS: Whole-body (18)F-FDG PET/CT imaging was performed in 52 patients with 125 lung lesions. (18)F-FDG PET was performed using optimized, amplitude-based respiratory gating. For CT, 36 patients were randomly assigned to the free-breathing (FB) group and 16 to the rest-expiratory breath-hold (BH) group. Spatial mismatch between the PET and CT images was quantified by measuring the distance between the centroids of PET and CT lesions and calculating the Jaccard similarity coefficient (JSC). RESULTS: In the upper lobes, the average distance between the centroids of the PET and CT lesions was 4.7 ± 3.1 and 6.0 ± 3.0 mm for the FB and BH groups, respectively (P = 0.11). For the middle and lower lobes, the distances were 5.8 ± 4.3 and 5.1 ± 2.9 mm (P = 0.70), respectively, and for the central region 4.8 ± 4.6 and 5.6 ± 2.0 mm (P = 0.24), respectively. The JSC for the upper lobes was 0.28 ± 0.17 and 0.28 ± 0.19, for the FB and the BH group, respectively (P = 0.83). For the middle and lower lobes, the JSC was 0.22 ± 0.16 and 0.28 ± 0.18 (P = 0.20), respectively, and for the central region 0.39 ± 0.17 and 0.13 ± 0.04 (P = 0.04), respectively. CONCLUSION: Providing breathing instructions to the patients during the CT acquisition did not improve the spatial alignment between the respiratory-gated PET images and the CT images. The difficulty experienced in using this clinical protocol, such as patient compliance and operator dependence, emphasizes the need for other strategies.

Using the NEMA NU 4 PET image quality phantom in multipinhole small-animal SPECT.

UNLABELLED: Several commercial small-animal SPECT scanners using multipinhole collimation are presently available. However, generally accepted standards to characterize the performance of these scanners do not exist. Whereas for small-animal PET, the National Electrical Manufacturers Association (NEMA) NU 4 standards have been defined in 2008, such standards are still lacking for small-animal SPECT. In this study, the image quality parameters associated with the NEMA NU 4 image quality phantom were determined for a small-animal multipinhole SPECT scanner. METHODS: Multiple whole-body scans of the NEMA NU 4 image quality phantom of 1-h duration were performed in a U-SPECT-II scanner using (99m)Tc with activities ranging between 8.4 and 78.2 MBq. The collimator contained 75 pinholes of 1.0-mm diameter and had a bore diameter of 98 mm. Image quality parameters were determined as a function of average phantom activity, number of iterations, postreconstruction spatial filter, and scatter correction. In addition, a mouse was injected with (99m)Tc-hydroxymethylene diphosphonate and was euthanized 6.5 h after injection. Multiple whole-body scans of this mouse of 1-h duration were acquired for activities ranging between 3.29 and 52.7 MBq. RESULTS: An increase in the number of iterations was accompanied by an increase in the recovery coefficients for the small rods (RC(rod)), an increase in the noise in the uniform phantom region, and a decrease in spillover ratios for the cold-air- and water-filled scatter compartments (SOR(air) and SOR(wat)). Application of spatial filtering reduced image noise but lowered RC(rod). Filtering did not influence SOR(air) and SOR(wat). Scatter correction reduced SOR(air) and SOR(wat). The effect of total phantom activity was primarily seen in a reduction of image noise with increasing activity. RC(rod), SOR(air), and SOR(wat) were more or less constant as a function of phantom activity. The relation between acquisition and reconstruction settings and image quality was confirmed in the (99m)Tc-hydroxymethylene diphosphonate mouse scans. CONCLUSION: Although developed for small-animal PET, the NEMA NU 4 image quality phantom was found to be useful for small-animal SPECT as well, allowing for objective determination of image quality parameters and showing the trade-offs between several of these parameters on variation of acquisition and reconstruction settings.

Influence of blood glucose level, age and fasting period on non-pathological FDG uptake in heart and gut.

PURPOSE: Increased, non-pathological FDG uptake in myocardium, stomach and bowel is frequently observed while performing clinical positron emission tomography (PET) studies. This "physiological" increased FDG uptake is not related to (oncological) disease and is unwanted since it may interfere with correct image reading. We evaluated the role of several patient-related factors that may have an influence on this phenomenon. METHODS: One hundred and seventy-five non-diabetic patients with malignant diseases, referred to our department for routine whole-body FDG-PET, were retrospectively evaluated. Age, blood glucose levels and duration of the fasting period were recorded. FDG uptake in myocardium, bowel and stomach was visually graded. RESULTS: Statistical analysis showed that increased FDG uptake in myocardium, bowel and stomach was not significantly correlated to blood glucose level, age or duration of fasting. Most patients who underwent repeated PET scans (92 scans in 25 patients), showed no or minor changes in uptake in bowel and stomach on the consecutive scans, while myocardial uptake was more variable. CONCLUSION: Age, fasting period and blood glucose levels did not influence physiological uptake. However, there seemed to be a patient-specific pattern for stomach and bowel uptake.